Uremia and dialysis are viewed as catabolic processes resulting in malnutrition in chronic renal failure (CRF) patients. To sort out the effects of uremia, acidosis and dialysis on protein metabolism, we measured leucine flux in CRF patients before and after initiation of maintenance dialysis. Whole body leucine flux was measured by primed-constant infusion of L[1-13C]leucine in 9 CRF patients longitudinally; twice before and once after initiation of maintenance dialysis [D]. Before dialysis, one leucine flux was measured when the patients were acidotic [A], and the other, when acidosis was corrected with NaHCO3[NA]. Five normal subjects underwent one single leucine flux measurement to serve as control [N]. Both patients and normal subjects consumed a constant diet for 6 days and leucine flux was measured on the 7th day 12 hr. post-absorption. Diet for the CRF patients was identical during the three periods. Plasma L[1-13C] leucine and L[1-13C]KIC were measured by gas c hromatography/mass spectrometry and expired 13CO2 by isotope ratio spectrometry. Leucine kinetics were calculated using standard equations. Plasma CO2 were 19,26 and 31 mmol/L in A, NA and D periods, respectively. All kinetic results ((mol/kg/hr) are presented as means (SD in the order of A, NA, D and N, and CRF values that are statistically different from N are identified [*]. The amount of leucine release from endogenous protein breakdown [Ra or Q] were 101(12*, 95(9*, 113(22 and 117(6. Leucine oxidation [C], quantity of leucine irreversibly oxidized to CO2, were 16.5(5.4, 9.7(3.7*, 12.3(3.0* and 23.2(3.1. Leucine protein incorporation [S] were 85(10, 85(8, 101(19 and 94(6. The S of 101 in CRF patients at period D was statistically higher than those during A and NA periods. These data indicate that when acidosis was corrected, CRF patients adapted to lower protein intake by reducing amino acid oxidation and protein degradation, and maintained protein synthesis at normal level . Metabolic acidosis impaired the down regulation of amino acid oxidation. Maintenance dialysis treatment longitudinally restored protein flux to normal and increased protein synthesis. The general notion that uremia and dialysis are protein catabolic are not supported by this work.